Lung cancer incidence and mortality in National Lung Screening Trial participants who underwent low-dose CT prevalence screening: a retrospective cohort analysis of a randomised, multicentre, diagnostic screening trial

Abstract

Background: Annual low-dose CT screening for lung cancer has been recommended for high-risk individuals, but the necessity of yearly low-dose CT in all eligible individuals is uncertain. This study examined rates of lung cancer in National Lung Screening Trial (NLST) participants who had a negative prevalence (initial) low-dose CT screen to explore whether less frequent screening could be justified in some lower-risk subpopulations.

Methods: We did a retrospective cohort analysis of data from the NLST, a randomised, multicentre screening trial comparing three annual low-dose CT assessments with three annual chest radiographs for the early detection of lung cancer in high-risk, eligible individuals (aged 55-74 years with at least a 30 pack-year history of cigarette smoking, and, if a former smoker, had quit within the past 15 years), recruited from US medical centres between Aug 5, 2002, and April 26, 2004. Participants were followed up for up to 5 years after their last annual screen. For the purposes of this analysis, our cohort consisted of all NLST participants who had received a low-dose CT prevalence (T0) screen. We determined the frequency, stage, histology, study year of diagnosis, and incidence of lung cancer, as well as overall and lung cancer-specific mortality, and whether lung cancers were detected as a result of screening or within 1 year of a negative screen. We also estimated the effect on mortality if the first annual (T1) screen in participants with a negative T0 screen had not been done. The NLST is registered with ClinicalTrials.gov, number NCT00047385.

Findings: Our cohort consisted of 26 231 participants assigned to the low-dose CT screening group who had undergone their T0 screen. The 19 066 participants with a negative T0 screen had a lower incidence of lung cancer than did all 26 231 T0-screened participants (371·88 [95% CI 337·97-408·26] per 100 000 person-years vs 661·23 [622·07-702·21]) and had lower lung cancer-related mortality (185·82 [95% CI 162·17-211·93] per 100 000 person-years vs 277·20 [252·28-303·90]). The yield of lung cancer at the T1 screen among participants with a negative T0 screen was 0·34% (62 screen-detected cancers out of 18 121 screened participants), compared with a yield at the T0 screen among all T0-screened participants of 1·0% (267 of 26 231). We estimated that if the T1 screen had not been done in the T0 negative group, at most, an additional 28 participants in the T0 negative group would have died from lung cancer (a rise in mortality from 185·82 [95% CI 162·17-211·93] per 100 000 person-years to 212·14 [186·80-239·96]) over the course of the trial.

Interpretation: Participants with a negative low-dose CT prevalence screen had a lower incidence of lung cancer and lung cancer-specific mortality than did all participants who underwent a prevalence screen. Because overly frequent screening has associated harms, increasing the interval between screens in participants with a negative low-dose CT prevalence screen might be warranted.

Funding: None.

Figure 1. Flow diagram of screen results in participants with a negative T0 screen

Interval and screen-detected lung cancers are defined as occurring within 12 months of the previous screen—eg, T2-interval lung cancers are those diagnosed in the 12 months after a negative or missed T2 screen. NLST=National Lung Screening Trial. T0=prevalence screen. T1=first annual screen. T2=second annual screen.

Figure 2. Cumulative incidence of lung cancer diagnosis, by screening result

Dotted lines show 95% CIs. T0=prevalence screen. T1=first annual screen. T2=second annual screen.

Figure 3. Lung cancer-free survival according to risk group

Kaplan-Meier curves (ie, time from T0 screen to date of diagnosis of lung cancer, death, or censoring, whichever came first) in participants with a negative T0 screen, stratified according to specific criteria: (A) age (<65 years vs ≥65 years); (B) smoking history (<45 pack-years vs ≥45 pack-years); (C) age younger than 65 years and smoking history (<45 pack-years vs ≥45 pack-years); and (D) history of chronic obstructive pulmonary disorder (COPD), age 65 years or older, and smoking history of 45 or more pack-years versus all other eligible participants. Dotted lines show 95% CIs.